Currently, the treatment of allergic disease is based on allergen avoidance, pharmacotherapy for symptom relief, and allergen-specific immunotherapy (SIT). SIT is the only treatment modality with the potential of altering the natural course of the disease by increasing immunological tolerance, thereby entailing sustained reductions in symptoms.
Subcutaneous allergen injections have been the main approach for conducting SIT, which include weekly to monthly subcutaneous injections to allergic patients with a selected allergen over an extended period of time (SCIT immunotherapy)
However, recently another route of administering the allergen has been proven effective, namely sublingual administration, which offers several advantages compared with the subcutaneous route, including increased convenience, compliance, and safety. For example, the risk of severe systemic allergic reactions following sublingual allergen-specific immunotherapy is considered as being low as the oromucosal administration of allergens does not lead to absorption into the vascular system to any significant extent. However, other mild to moderate side reactions are still seen in some patients, e.g. in the form of local allergic reactions, oral itching and sublingual oedema. Sublingual allergen-specific immunotherapy (SLIT) is today carried out by administering the allergen in liquid dosage form (droplets or spray) or in solid dosage form (tablet).
For reasons of safety, specific-allergen-specific immunotherapy has conventionally been performed with a dosing regimen that is divided in two consecutively treatment phases, namely an up-dosing phase where increasing doses are administered until an effective and safe treatment dose has been reached, which dose is used throughout the maintenance phase. Typically, the up-dosing phase in SCIT comprises weekly injections over a 4 months period and the maintenance phase comprises monthly injections. With SLIT, the up-dosing phase may be conducted over a shorter period and doses are administered more frequently.
Current knowledge suggests that success of allergen-specific immunotherapy depends on the cumulative dose of allergen administered (Kopp and Heinzmann, Applikationsformen der spezifiscien Immuntherapie, Allergo J 16, 570-5, 2007). Therefore, faster up-dosing phases, such as over a 5 days-period (Rush up-dosing phase) or over even fewer days (Ultra-Rush up-dosing phase) with higher doses of allergen have been applied in some circumstances. Up-dosing is also applied with sublingual administration of allergen in liquid dosage form (table 2 in Kopp and Heinzmann 2007).
With respect to allergen-specific immunotherapy with seasonal allergens, such as allergens derived from pollen, there is an additional precaution to make in conducting SIT. Currently, to avoid an exaggerated allergen load it is required to start the allergen-specific immunotherapy at least 2-4 months prior to the pollen season. This requirement of initiating immunotherapy prior to the pollen season is based on the fact that during the pollen season the immune system of an allergic subject is already “primed” by pollen in the air and this may lead to the occurrence of more adverse events related to treatment when treatment is initiated during this period. For example, in current approved SLIT, the sublingual administration of the allergen in tablet formulation comprises no up-dosing phase, but the immunotherapy has to be initiated 4 months before the pollen season (table 2 in Kopp and Heinzmann 2007).
However, many subjects have their first visit to the physician concerning their allergic complaints when they experience the symptoms, i.e. during the pollen season, and today, these subjects can only be offered symptomatic therapy. Usually, subjects are told to return after the pollen season to start immunotherapy, but this rarely happens because they forget the appointment once they do not experience the symptoms anymore. Presently, these subjects can only be offered symptomatic therapy based on the recommendation described above.
Therefore, there is still a need for improved allergen-specific immunotherapy, where more patients can benefit to safe and effective treatment.
Seidenberg et al. (Clinical and Experimental Allergy, 36, 1201-1212, British Society for Allergy and Clinical Immunology, Annual Conference—July 2006, Abstract S17) describes immunotherapy treatment of children with a liquid allergy vaccine comprising a seasonal allergen that is administered sublingually and includes an up-dosing phase that is initiated shortly before the start of the season or during the season.
DE Utility Model 20 2007 004 567.0 discloses allergen-specific immunotherapy with seasonal allergen by parenteral administration, wherein the dosage regimen comprises an up-dosing phase that is initiated after start of the pollen season.
WO 2007/051476 discloses the use of an allergen for the manufacture of a liquid vaccine formulation for preventing or treating allergy in a subject by oromucosal administration in a dosage regimen comprising no up-dosing.
Ronald Dahl et al (in sublingual grass allergen-specific immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years, J Allergy Clin Immunol vol 121, No 2, p 512-518, 2007) discloses allergen-specific immunotherapy with a solid dosage form comprising a seasonal allergen that is administered sublingually in a daily dosing regimen where immunotherapy was initiated 4-8 months before the anticipated start of the grass pollen season and treatment was continued after end of the grass pollen season.